In the medical arts, there are known certain medicinal storage bottles useful for storing, shipping and containing a medicine disposed in dry powder or tablet form that is intended to be reconstituted with a liquid substance for administration to a patient. Examples of such containers are found, inter alia, in U.S. Pat. Nos. 3,033,202 to Richter et al.; 3,206,073 to Scislowicz; 4,211,333 to Villarejos; and 4,941,876, 5,358,501 and PCT Application WO 90/07319, all to Meyer or Meyer et al. Utilizing the Scislowicz patent as a reference and as depicted in FIGS. 1 and 2 of that patent, common to all the devices disclosed in the prior art there includes some type of container 10 containing a medicament 14 to be reconstituted. Access to a reconstituting fluid 37 held in a separate container 35 is provided by a transfer assembly 13. In the Scislowicz reference, the transfer assembly includes a sharpened cannula element, but in the case of the Meyer et al. U.S. '876 and PCT '319 references, the transfer assembly includes some type of Luer-Lock adapter suitable for connection directly with other bottles (for instance, PCT '319) or with a separate needle cannula element (U.S. '876).
As the skilled artisan will appreciate, the sterility of the medicinal component 14 held in the container 10 is normally preserved by some type of sealing mechanism, isolating at least the medicament 14 from contamination with the outside environment. In a number of these assemblies, such as the Scislowicz '073 patent or the Meyer '501 patent, sealing isolation for the medicament is provided by incorporating as part of the transfer assembly some type of sealing mechanism slidably engageable with the neck of the bottle, itself incorporating a fluid conduit selectably in fluid communication with the interior of the bottle. The transfer assembly can thus be slid downwards towards the interior of bottle when lyophilization of the medicament is desired. However, during transport of the bottle, the sealing portion is retained in the neck, in an attempt to block the fluid conduit and cut off any environmental contact with the interior of the bottle through the transfer assembly.
In a similar vein, separate seal portions are often incorporated about the transfer assembly to further enhance the imperviousness of the aforementioned designs to extraneous contamination. For example, in the Meyer '501 patent, a toroidally-shaped sealing element 29 is incorporated which contacts the interior neck portion of the container 10 so as to form an aseptic barrier during storage, as well as to provide a sealed connection and an aseptic barrier during the activation phase of the container. In addition, as evident from the Scislowicz or Meyer references, a removable cap element 40 is often fitted about the transfer assembly 13 in an effort to protect the transfer assembly from damage or contaminating contact pending use of the container. The cap, often configured to be retained with or against a portion of the container 10, can be covered with a tamper-evident seal (such as seen in Meyer '501) so as to give further indication if the sterility of the medicament 14 might have been somehow compromised.
While the foregoing approaches in general are directed to preserving the sterility of the medicament 14 held within the container, discrepancies in dimensions or manufacturing tolerances of the various components forming the medicinal storage bottles, the handling of the bottles during shipment by ground, sea or air, and related factors could affect the ability of the bottles to maintain sterility of the medicament 14 pending use. Tests for integrity include, inter alia, immersing the bottle in a fluid bath over a set period of time, with the fluid held at pressures simulating conditions to which the bottle will be exposed over time.
In particular, while for the most part serving to isolate the medicament itself from external contaminant effects, it has been found that contaminants of liquid, biological, or particulate nature may still be able to infiltrate the container through the cap element 40, thereby contaminating the transfer assembly 13. Difficulties associated with molding the interface between cap and container with a perfectly precise fit make it virtually impossible to ensure sterility relying solely on the cap as a barrier. More specifically, dimensional variations are bound to occur from production batch to batch, so that a hermetic seal between matching components cannot be assured in every instance. In addition, molded parts sometimes display weld lines which, if disposed in an area necessitating perfect mating contact, can interfere with precise fit. Overall then, most molding techniques cannot be relied upon to produce seals of a hermetic nature. This, more often than not, is an unacceptable condition for a product relying on sterility prior to use.
The above-mentioned difficulties are further amplified by the treatment imposed on the bottles during shipment. For example, the bottles may be exposed to extreme atmospheric variations, inclusive of temperature extremes and, when shipment occurs by air, significant pressure disturbances. Such changes in pressure or temperature act upon the individual components and normally cause any hermetic seals effected by precision molding to be disrupted or broken, exposing the bottle and particularly the transfer assembly to contamination. Absent a proper seal impervious to atmospheric variations, shipment is oftentimes limited to road or rail transport, which is slower and sometimes costlier than shipment by air.
Moreover, owing to considerations of cost, manufacturing efficiencies, and ease of transport, it is common for relatively bulky items such as medicinal storage bottles to be shipped only in simple corrugated or cardboard containers, which provide little if any protection against exposure to outside contaminants. Blister packs or pouches, typically employed when an enclosed product is sterilized such as by gas treatment or irradiation, are normally excluded from bulky product such as medical storage bottles. Thus, there is usually the requirement for the bottle to rely solely on its own integral design and its components for maintaining the sterility of the product contained therein.
There is a need, therefore, for a way to ensure sterility in a medicinal storage bottle, relying on its integral componentry and design, which is particularly impervious to handling or shipment conditions to which the bottle is exposed, and which accounts for tolerance or dimensional variations in the components forming the bottle.